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Estradiol: 6 things you should know

Written by C. Fookes, BPharm on Nov 23, 2018

1. How it works

  • Estradiol is the principal intracellular human estrogen. In women with menstrual periods, 70 to 500mcg of natural estradiol is secreted daily, depending on the phase of the menstrual cycle. After menopause, the adrenal cortex secretes a precursor to estrogen called androstenedione, which is converted by peripheral tissues into estrone, which is the most abundant circulating estrogen in postmenopausal women.
  • All estrogens act by binding to estrogen receptors in estrogen-responsive tissues. Estrogens work by a negative feedback mechanism to reduce circulating levels of gonadotrophins, luteinizing hormone (LH) and follicle stimulating hormone (FSH) in postmenopausal women.
  • Estradiol belongs to the class of medicines called estrogens.

2. Upsides

  • May be used for the treatment of moderate to severe vasomotor symptoms (eg, hot flashes/flushes), and vulvar and vaginal atrophy associated with menopause. However, topical estrogen products are preferred if just prescribing for vulvar and vaginal atrophy.
  • Treats low estrogen levels associated with hypogonadism, castration or primary ovarian failure.
  • May be used in appropriate patients for the palliative care of breast cancer in women or men with metastatic disease.
  • May be used in the palliation of advanced androgen-dependent prostate cancer.
  • May be considered for the prevention of postmenopausal osteoporosis in women at significant risk and for whom non-estrogen treatments are not appropriate. However, the 2017 American College of Physicians (ACP) guidelines do not recommend its use for this indication.
  • Generic estradiol is available.

3. Downsides

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

  • Bleeding changes, an increase in the incidence of vaginal candidiasis, breast pain and discharge, high blood pressure, nausea, vomiting, abdominal cramps, scalp hair loss, hirsutism, headache, mood disturbances, weight changes, fluid retention, skin changes, or an exacerbation of endometriosis. Estradiol may also exacerbate pre-existing conditions such as asthma, diabetes, epilepsy, and migraine and interfere with some laboratory tests.
  • Estrogens are associated with an increased risk of endometrial cancer. All persistent or recurrent abnormal vaginal bleeding should be investigated, and endometrial sampling undertaken when indicated.
  • An increased risk of heart attack (myocardial infarction), stroke, invasive breast cancer, pulmonary emboli and deep vein thrombosis have been associated with estrogen use (including estradiol), with or without progestins. An increased risk of dementia has also been reported in postmenopausal women 65 years of age or older.
  • Estrogens, with or without progestins should be prescribed at the lowest effective dose for the shortest possible time.
  • With regards to osteoporosis, estradiol has been shown to prevent vertebral bone loss in postmenopausal women. However, it does not restore bone mass to premenopausal levels and once discontinued, bone loss reverts back to the immediate postmenopausal period. The 2017 ACP guidelines for the treatment of osteoporosis do not recommend estrogen therapy for postmenopausal women with established osteoporosis.
  • Should not be used in women with undiagnosed abnormal genital bleeding, with a known or suspected history of breast cancer except in appropriate patients when used for palliation, with estrogen-dependent cancer, with active deep vein thrombosis, pulmonary embolism or a history of these conditions. Estradiol is also not suitable for people with a recent history of stroke or a heart attack or other thromboembolic disease, liver disease, or known or suspected pregnancy.
  • Estrogen use is associated with a two to four-fold increased risk in gallbladder disease requiring surgery. It may also lead to severe high calcium levels in patients with breast cancer or bone metastases. Visual abnormalities have also been reported.
  • In women who have not had a hysterectomy, the addition or progestin for 10 days each cycle lowers the risk of endometrial hyperplasia (may be a precursor to endometrial cancer).
  • Blood pressure and cholesterol/triglyceride levels should be monitored regularly throughout estrogen therapy.
  • People with hypothyroidism receiving replacement therapy may require increased doses of thyroid replacement therapy when taking estrogens.

Notes: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. For a complete list of all side effects, click here.

4. Bottom Line

Estradiol is a synthetic form of estrogen that may be given to women for a number of different indications, including the relief of menopausal symptoms or low estrogen levels. Its use is associated with an increased risk of endometrial and breast cancer and cardiovascular disease. The ACP no longer recommend estrogens for the treatment of postmenopausal osteoporosis.

5. Tips

  • Take estradiol exactly as directed by your doctor. The dosage varies depending on what you are taking estradiol for. Do not increase or decrease the dose unless instructed to do so. You should only take estradiol for short periods of time when used to treat menopausal symptoms. Talk to your doctor about this
  • Your doctor may add a progestin to your estradiol therapy. This is to reduce the risk of changes to your endometrium.
  • Report any unusual vaginal bleeding, heart pain, breast lumps, dizziness, severe headaches, shortness of breath, changes in vision, leg pains, or changes in your speech or skin to your doctor immediately.
  • There is an increased risk of cancer associated with estradiol use. Discuss this with your doctor.
  • Keep your scheduled appointments with your doctor. it is important you go for a checkup at least once a year. Ensure you go for your recommended screenings (eg, mammograms).
  • If you smoke, have high blood pressure, diabetes, are overweight, or have high cholesterol your risk of heart disease associated with estradiol use is increased.
  • Keep estradiol tablets out of reach of children. Do not share your tablets with anybody else.

6. Response and Effectiveness

  • Estradiol is substantially more potent than its metabolites, estrone and estriol at the estrogen receptor level.
  • Estradiol is commonly synthesized as a prodrug ester (for example, estradiol acetate, estradiol valerate) to improve its bioavailability. Ethinylestradiol is a synthetic form of estradiol that is commonly used in oral contraceptives because it is absorbed better and is not so easily metabolized.

References

Estradiol [Package insert] 10/2018 EPIC PHARMA, LLC https://www.drugs.com/pro/estradiol.html

Further information

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use estradiol only for the indication prescribed.

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Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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